In the fields of medicine and physiology, an accurate assessment of renal function is essential for diagnosis and evaluation of the progression of acute and chronic injuries to the kidneys. During the course of chronic renal disease, the rate of loss of renal function is generally constant. Decreasing function has been shown to occur because of damage to the individual filtration units of each kidney, known as nephrons. Each kidney has approximately 10.sup.6 nephrons.
In discussing the prognosis and therapy for patients with chronic renal failure (CRF), the residual value of a glomerular filtration rate (GFR) is typically used. The GFR represents the sum total volume of whole blood filtrate which is processed by the glomeruli of both kidneys. For a healthy adult the GFR typically ranges from 120 to 125 ml/min filtered.
Several methods are used to estimate GFR under standard conditions. One method utilizes an intravenous infusion of inulin to measure inulin clearance as an estimate of GFR. The inulin must be carefully regulated to maintain a constant plasma concentration of drug while a timed urine sample is collected, usually over a 24-hour period. Timed urine sample collection is typically inaccurate due to daily variations in urine flow, incomplete emptying of the bladder, and partial loss of the sample. Under optimal conditions, the coefficient of variation (CV) for inulin clearance as compared to GFR is approximately 10 percent in healthy patients and higher in patients with CRF or other severe illnesses.
Another method for estimating GFR employs various radiolabled compounds that are eliminated by glomerular filtration only. Most of these compounds are gamma-emitters, thereby avoiding the error caused by variable quenching in plasma and urine samples as occurs with beta-emitters. While this method is easier to use than the inulin method and has similar CV (10-17 percent), it presents radiation-safety hazards and many practical considerations.
Due to the difficulties inherent in the above methods for estimating GFR, clinicians have relied instead upon measuring creatinine clearances. Creatinine, a waste product of muscle metabolism, is a metabolic side-product occurring in parallel to phosphorocreatine metabolism. Phosphorocreatine is produced from creatine. Creatine is manufactured in the liver from glycine and arginine, transferred to skeletal muscle and converted to the energy-rich compound phosphorocreatine. As creatine cycles between itself and phosphorocreatine in muscle, a small amount of creatine is irreversibly converted to creatinine which is excreted through the kidneys.
The 24-hour creatinine clearance slightly exceeds inulin clearance due to tubular secretion of creatinine in the proximal tubules of each nephron. This method, while not requiring the introduction of an exogenous substance into the patient, does require venipuncture for a blood sample and timed urine sample collection. Consequently, this method is also highly susceptible to errors in timed urine sample collection as discussed above with regard to the inulin clearance method. Estimates for day-to-day variability in ambulatory patients are typically as high as 26 percent. Some portion of this variability is due to daily variations in creatinine metabolism, but the majority is due to urine collection difficulties.
Although estimates for GFR are easier with creatinine than inulin, such procedures are not amenable to routine patient screening due to the necessity of collecting a large volume of urine, usually over a 24 hour period. Consequently, patients are generally only screened for renal function after they develop physical symptoms ascribable to renal dysfunction. This oftentimes allows occult damage to occur that was potentially preventable.
Thus, there exists a need for a simplified method of routinely monitoring patients for renal dysfunction without the necessity for timed urine sample collections and employment of exogenous substances. Accordingly, it is to the provision of such an improved method that the present invention is primarily directed.